The biologic, functional and chemical characterization of human lymphoid cell surface antigens are under investigation. Methods for rapidly isolating subpopulations of lymphocytes (B cells, monocytes, K cells, T cells) have been developed. Monocytes share B cell alloantigens as do skin macrophages. Multiple genes control the expression of B cell alloantigens and are linked to genes controlling HLA antigens. Studies of two autoimmune diseases, Sicca syndrome and SLE have demonstrated a complex of B cell alloantigens occuring in greater frequency compared to the normal populations, suggesting an autoimmune response gene. The B cell alloantigens of man and mice appear to have arisen from a common ancestral gene by two criteria: 1) antisera detecting murine Ia antigens also react with human B cell antigens precipitating components with similar molecular weights; 2) amino acid sequence of the 34,000 molecular weight chain bearing human B cell alloantigenic determinants is nearly identical sequence with that reported for the murine Ia antigen. Chemical analysis of the HLA alloantigens have demonstrated 5 major peptides. Different HLA alloantigen molecules have demonstrated near complete amino acid sequence homology save for a variable region surrounding a cystine peptide.